title: Function of site-2 proteases in bacteria and bacterial pathogens.
abstract: Site-2 proteases (S2Ps) are a class of intramembrane metalloproteases named after the founding member of this protein family, human S2P, which control cholesterol and fatty acid biosynthesis by cleaving Sterol Regulatory Element Binding Proteins which control cholesterol and fatty acid biosynthesis. S2Ps are widely distributed in bacteria and participate in diverse pathways that control such diverse functions as membrane integrity, sporulation, lipid biosynthesis, pheromone production, virulence, and others. The most common signaling mechanism mediated by S2Ps is the coupled degradation of transmembrane anti-Sigma factors to activate ECF Sigma factor regulons. However, additional signaling mechanisms continue to emerge as more prokaryotic S2Ps are characterized, including direct proteolysis of membrane embedded transcription factors and proteolysis of non-transcriptional membrane proteins or membrane protein remnants. In this review we seek to comprehensively review the functions of S2Ps in bacteria and bacterial pathogens and attempt to organize these proteases into conceptual groups that will spur further study. This article is part of a Special Issue entitled: Intramembrane Proteases.
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, USA; Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Biomedical Sciences, USA.
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Schneider
authors.forename: Michael S
authors.initials: MS
authors.lastname: Glickman
mesh_terms: D001426:Bacterial Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006090:Gram-Negative Bacteria / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D006094:Gram-Positive Bacteria / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010675:Pheromones / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D015398:Signal Transduction; D013379:Substrate Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D010675:Pheromones; D014157:Transcription Factors; D037521:Virulence Factors; D008666:Metalloendopeptidases
keywords: Bacterial signal transduction; Site two protease